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Purpose: Proton beam therapy (PBT) plays an important role in the management of primary spine tumors. The purpose of this consensus statement was to summarize safe and optimal delivery of PBT for spinal tumors., Methods and Materials: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee consisting of radiation oncologists and medical physicists with specific expertise in spinal irradiation developed expert recommendations discussing treatment planning considerations and current approaches in the treatment of primary spinal tumors., Results: Computed tomography simulation: factors that require significant consideration include (1) patient comfort, (2) setup reproducibility and stability, and (3) accessibility of appropriate beam angles., Spine Stabilization Hardware: If present, hardware should be placed with cross-links well above/below the level of the primary tumor to reduce the metal burden at the level of the tumor bed. New materials that can reduce uncertainties include polyether-ether-ketone and composite polyether-ether-ketone-carbon fiber implants., Field Arrangement: Appropriate beam selection is required to ensure robust target coverage and organ at risk sparing. Commonly, 2 to 4 treatment fields, typically from posterior and/or posterior-oblique directions, are used., Treatment Planning Methodology: Robust optimization is recommended for all pencil beam scanning plans (the preferred treatment modality) and should consider setup uncertainty (between 3 and 7 mm) and range uncertainty (3%-3.5%). In the presence of metal hardware, use of an increased range uncertainty up to 5% is recommended., Conclusions: The Particle Therapy Cooperative Group Skull Base/Central nervous system/Sarcoma Subcommittee has developed recommendations to enable centers to deliver PBT safely and effectively for the management of primary spinal tumors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Experimental patient-specific QA (PSQA) is a time and resource-intensive process, with a poor sensitivity in detecting errors. Radiation therapy facilities aim to substitute it by means of independent dose calculation (IDC) in combination with a comprehensive beam delivery QA program. This paper reports on the commissioning of the IDC software tool myQA iON (IBA Dosimetry) for proton therapy and its clinical implementation at the MedAustron Ion Therapy Center., Methods: The IDC commissioning work included the validation of the beam model, the implementation and validation of clinical CT protocols, and the evaluation of patient treatment data. Dose difference maps, gamma index distributions, and pass rates (GPR) have been reviewed. The performance of the IDC tool has been assessed and clinical workflows, simulation settings, and GPR tolerances have been defined., Results: Beam model validation showed agreement of ranges within ± 0.2 mm, Bragg-Peak widths within ± 0.1 mm, and spot sizes at various air gaps within ± 5% compared to physical measurements. Simulated dose in 2D reference fields deviated by -0.3% ± 0.5%, while 3D dose distributions differed by 1.8% on average to measurements. Validation of the CT calibration resulted in systematic differences of 2.0% between IDC and experimental data for tissue like samples. GPRs of 99.4 ± 0.6% were found for head, head and neck, and pediatric CT protocols on a 2%/2 mm gamma criterion. GPRs for the adult abdomen protocol were at 98.9% on average with 3%/3 mm. Root causes of GPR outliers, for example, implants were identified and evaluated., Conclusion: IDC has been successfully commissioned and integrated into the MedAustron clinical workflow for protons in 2021. IDC has been stepwise and safely substituting experimental PSQA since February 2021. The initial reduction of proton experimental PSQA was about 25% and reached up to 90% after 1 year., (© 2024 The Authors. Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Purpose: Intracerebral radiation-induced contrast enhancement (RICE) can occur after photon as well as proton beam therapy (PBT). This study evaluated the incidence, characteristics, and risk factors of RICE after PBT delivered to, or in direct proximity to, the brain and its effect on health-related quality of life (HRQoL)., Methods and Materials: Four hundred twenty-one patients treated with pencil beam scanning PBT between 2017 and 2021 were included. Follow-up included clinical evaluation and contrast-enhanced magnetic resonance imaging at 3, 6, and 12 months after treatment completion and annually thereafter. RICE was graded according to Common Terminology Criteria for Adverse Events version 4, and HRQoL parameters were assessed via European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 questionnaires., Results: The median follow-up was 24 months (range, 6-54), and median dose to 1% relative volume of noninvolved central nervous system (D1%CNS) was 54.3 Gy relative biologic effectiveness (RBE; range, 30-76 Gy RBE). The cumulative RICE incidence was 15% (n = 63), of which 10.5% (n = 44) were grade 1, 3.1% (n = 13) were grade 2, and 1.4% (n = 6) were grade 3. No grade 4 or 5 events were observed. Twenty-six of 63 RICE (41.3%) had resolved at the latest follow-up. The median onset after PBT and duration of RICE in patients in whom the lesions resolved were 11.8 and 9.0 months, respectively. On multivariable analysis, D1%CNS > 57.6 Gy RBE, previous in-field radiation, and diabetes mellitus were identified as significant risk factors for RICE development. Previous radiation was the only factor influencing the risk of symptomatic RICE. After PBT, general HRQoL parameters were not compromised. In a matched cohort analysis of 54/50 patients with and without RICE, no differences in global health score or functional and symptom scales were seen., Conclusions: The overall incidence of clinically relevant RICE after PBT is very low and has no significant negative effect on long-term patient QoL., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this work is to present the first microdosimetric spectra measured with a miniaturised tissue-equivalent proportional counter in the clinical environment of the MedAustron ion-beam therapy facility. These spectra were gathered with a 62.4-MeV proton beam and have been compared with microdosimetric spectra measured in the 62-MeV clinical proton beam of the CATANA beam line. Monte Carlo simulations were performed using the Geant4 toolkit GATE and a fully commissioned clinical beam line model. Finally, similarities and discrepancies of the measured data to simulations based on a simple and complex detector geometry are discussed., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction: A growing interest in using proton pencil beam scanning in combination with collimators for the treatment of small, shallow targets, such as ocular melanoma or pre-clinical research emerged recently. This study aims at demonstrating that the dose of a synchrotron-based PBS system with a dedicated small, shallow field nozzle can be accurately predicted by a commercial treatment planning system (TPS) following appropriate tuning of both, nozzle and TPS., Materials: A removable extension to the clinical nozzle was developed to modify the beam shape passively. Five circular apertures with diameters between 5 to 34mm, mounted 72cm downstream of a range shifter were used. For each collimator treatment plans with spread-out Bragg peaks (SOBP) with a modulation of 3 to 30mm were measured and calculated with GATE/Geant4 and the research TPS RayStation (RS11B-R). The dose grid, multiple coulomb scattering and block discretization resolution were varied to find the optimal balance between accuracy and performance., Results: For SOBPs deeper than 10mm, the dose in the target agreed within 1% between RS11B-R, GATE/Geant4 and measurements for aperture diameters between 8 to 34mm, but deviated up to 5% for smaller apertures. A plastic taper was introduced reducing scatter contributions to the patient (from the pipe) and improving the dose calculation accuracy of the TPS to a 5% level in the entrance region for large apertures., Conclusion: The commercial TPS and GATE/Geant4 can accurately calculate the dose for shallow, small proton fields using a collimator and pencil beam scanning., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Martin Janson reports a relationship with RaySearch Laboratories AB, Sweden that includes employment. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

In radiotherapy, radiation-quality should be an expression of the biological and physical characteristics of ionizing radiation such as spatial distribution of ionization or energy deposition. Linear energy transfer (LET) and lineal energy (y) are two descriptors used to quantify the radiation quality. These two quantities are connected and exhibit similar features. In ion-beam therapy (IBT), lineal energy can be measured with microdosimeters, which are specifically designed to cope with the high fluence of particles in clinical beams, while the quantification of LET is generally based on calculations. In pre-clinical studies, microdosimetric spectra are used for the indirect determination of relative biological effectiveness (RBE), e.g., using the microdosimetric kinetic model (MKM) or biophysical response functions. In this context it is important to consider saturation effects, which occur when the highest values of y become less biologically relevant compared to the relative contribution they make to the physical dose. Recent clinical data suggests that local tumor control and normal tissue effects can be linked to macroscopic and microscopic dosimetry parameters. In particular, positive clinical outcomes have been correlated to the highest LET values in the density distribution, and there is no evident link to the saturation discussed above. A systematic collection of microdosimetric information in combination with clinical data in retrospective studies may clarify the role of radiation quality at the highest LET. In the clinical setting, microdosimetry is not widely used yet, despite its potential to be linked with LET by experimentally-determined y values. Through this connection, both play an important role in complex therapy techniques such as intensity modulated particle therapy (IMPT), LET-painting and multi-ion optimization. This review summarizes the current state of microdosimetry for IBT and its potential, as well as research and development needed to make experimental microdosimetry a mature procedure in a clinical context., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Reporting on the first implementation of a proton dedicated commercial device (IBA Sphinx/Lynx) for daily Quality Assurance (QA) of scanned proton and carbon ion beams., Methods: Daily QA trendlines over more than 3 years for protons and more than 2 years for carbon ions have been acquired. Key daily QA parameters were reviewed, namely the spot size and position, beam range, Bragg peak width, coincidence (between beam and imaging system isocenters), homogeneity and dose., Results: The performance of the QA equipment for protons and carbon ions was evaluated. Daily QA trendlines allowed us to detect machine performance drifts and changes. The definition of tolerances and action levels is provided and compared with levels used in the literature., Conclusion: The device has been successfully implemented for routine daily QA activities in a dual particle therapy facility for more than 2 years. It improved the efficiency of daily QA and provides a comprehensive QA process., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Purpose: Overexpression of the somatostatin receptor (SSTR) has led to adoption of SSTR PET/CT for diagnosis and radiotherapy planning in meningioma, but data on SSTR expression during follow-up remain scarce. We investigated PET/CT quantifiers of SSTR tracers in WHO grade I meningioma following fractionated proton beam therapy (PBT) compared to standard response assessment with MRI., Methods: Twenty-two patients diagnosed with low-grade meningioma treated by PBT were included. Follow-up included clinical visits, MRI, and [ 68 Ga]Ga-DOTATOC PET/CT scans. Radiologic tumor response, MRI and PET volume (V MRI and V PET ), maximum and mean standardied uptake value (SUVmax/SUVmean), total lesion activity (TLA), and heterogeneity index (HI) were evaluated., Results: Median follow-up was 35.3 months (range: 6.4-47.9). Nineteen patients (86.4%, p = 0.0009) showed a decrease of SUVmax between baseline and first follow-up PET/CT (median: -24%, range: -53% to +89%) and in 81.8% of all cases, the SUVmax, SUVmean, and TLA at last follow-up were eventually lower than at baseline (p = 0.0043). Ambiguous trends without significance between the timepoints analyzed were observed for V PET . HI increased between baseline and last follow-up in 75% of cases (p = 0.024). All patients remained radiologically and clinically stable. Median V MRI decreased by -9.3% (range 0-32.5%, p < 0.0001) between baseline and last follow-up., Conclusion: PET/CT in follow-up of irradiated meningioma showed an early trend towards decreased binding of SSTR-specific tracers following radiation and MRI demonstrated consistently stable or decreasing tumor volume. Translational research is needed to clarify the underlying biology of the subsequent increase in SSTR PET quantifiers., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The increasing number of studies dealing with linear energy transfer (LET)-based evaluation and optimization in the field of carbon ion radiotherapy (CIRT) indicates the rising demand for LET implementation in commercial treatment planning systems (TPS). Benchmarking studies could play a key role in detecting (and thus preventing) computation errors prior implementing such functionalities in a TPS., Purpose: This in silico study was conducted to benchmark the following two LET-related functionalities in a commercial TPS against Monte Carlo simulations: (1) dose averaged LET (LET d ) scoring and (2) physical dose filtration based on LET for future LET-based treatment plan evaluation and optimization studies., Methods: The LET d scoring and LET-based dose filtering (in which the deposited dose can be separated into the dose below and above the user specified LET threshold) functionalities for carbon ions in the research version RayStation (RS) 9A-IonPG TPS (RaySearch Laboratories, Sweden) were benchmarked against GATE/Geant4 simulations. Pristine Bragg peaks (BPs) and cuboid targets, positioned at different depths in a homogeneous water phantom and a setup with heterogeneity were used for this study., Results: For all setups (homogeneous and heterogeneous), the mean absolute (and relative) LET d difference was less than 1 keV/ μ $\umu$ m (3.5%) in the plateau and target and less than 2 keV/ μ $\umu$ m (8.3%) in the fragmentation tail. The maximum local differences were 4 and 6 keV/ μ $\umu$ m, respectively. The mean absolute (and relative) physical dose differences for both low- and high-LET doses were less than 1 cGy (1.5%) in the plateau, target and tail with a maximum absolute difference of 2 cGy., Conclusions: No computation error was found in the tested functionalities except for LET d in lateral direction outside the target, showing the limitation of the implemented monochrome model in the tested TPS version., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

A magnetic resonance imaging (MRI) sequence independent deep learning technique was developed and validated to generate synthetic computed tomography (sCT) scans for MR guided proton therapy. 47 meningioma patients previously undergoing proton therapy based on pencil beam scanning were divided into training (33), validation (6), and test (8) cohorts. T 1 , T 2 , and contrast enhanced T 1 (T1CM) MRI sequences were used in combination with the planning CT (pCT) data to train a 3D U-Net architecture with ResNet-Blocks. A hyperparameter search was performed including two loss functions, two group sizes of normalisation, and depth of the network. Training outcome was compared between models trained for each individual MRI sequence and for all sequences combined. The performance was evaluated based on a metric and dosimetric analysis as well as spot difference maps. Furthermore, the influence of immobilisation masks that are not visible on MRIs was investigated. Based on the hyperparameter search, the final model was trained with fixed features per group for the group normalisation, six down-convolution steps, an input size of 128×192×192, and feature loss. For the test dataset for body/bone the mean absolute error (MAE) values were on average 79.8/216.3Houndsfield unit (HU) when trained using T1 images, 71.1/186.1HU for T2, and 82.9/236.4HU for T1CM. The structural similarity metric (SSIM) ranged from 0.95 to 0.98 for all sequences. The investigated dose parameters of the target structures agreed within 1% between original proton treatment plans and plans recalculated on sCTs. The spot difference maps had peaks at ±0.2cm and for 98% of all spots the difference was less than 1cm. A novel MRI sequence independent sCT generator was developed, which suggests that the training phase of neural networks can be disengaged from specific MRI acquisition protocols. In contrast to previous studies, the patient cohort consisted exclusively of actual proton therapy patients (i.e. "real-world data")., (Copyright © 2021. Published by Elsevier GmbH.)

Purpose: An independent dosimetry audit based on end-to-end testing of the entire chain of radiation therapy delivery is highly recommended to ensure consistent treatments among proton therapy centers. This study presents an auditing methodology developed by the MedAustron Ion Beam Therapy Center (Austria) in collaboration with the National Physical Laboratory (UK) and audit results for five scanned proton beam therapy facilities in Europe., Methods: The audit procedure used a homogeneous and an anthropomorphic head phantom. The phantoms were loaded either with an ionization chamber or with alanine pellets and radiochromic films. Homogeneously planned doses of 10Gy were delivered to a box-like target volume in the homogeneous phantom and to two clinical scenarios with increasing complexity in the head phantom., Results: For all tests the mean of the local differences of the absolute dose to water determined with the alanine pellets compared to the predicted dose from the treatment planning system installed at the audited institution was determined. The mean value taken over all tests performed was -0.1±1.0%. The measurements carried out with the ionization chamber were consistent with the dose determined by the alanine pellets with a mean deviation of -0.5±0.6%., Conclusion: The developed dosimetry audit method was successfully applied at five proton centers including various "turn-key" Cyclotron solutions by IBA, Varian and Mevion. This independent audit with extension to other tumour sites and use of the correspondent anthropomorphic phantoms may be proposed as part of a credentialing procedure for future clinical trials in proton beam therapy., (Copyright © 2021. Published by Elsevier GmbH.)

Purpose: This paper presents a novel method for the calculation of three-dimensional (3D) Bragg-Gray water-to-detector stopping power ratio (s w,det ) distributions for proton and carbon ion beams., Methods: Contrary to previously published fluence-based calculations of the stopping power ratio, the s w,det calculation method used in this work is based on the specific way GATE/Geant4 scores the energy deposition. It only requires the use of the so-called DoseActor, as available in GATE, for the calculation of the s w,det at any point of a 3D dose distribution. The simulations are performed using GATE-RTion v1.0, a dedicated GATE release that was validated for the clinical use in light ion beam therapy., Results: The Bragg-Gray water-to-air stopping power ratio (s w,air ) was calculated for monoenergetic proton and carbon ion beams with the default stopping power data in GATE-RTion v1.0 and the new ICRU90 recommendation. The s w,air differences between the use of the default and the ICRU90 configuration were 0.6% and 5.4% at the physical range (R 80 - 80% dose level in the distal dose fall-off) for a 70 MeV proton beam and a 120 MeV/u carbon ion beam, respectively. For protons, the s w,det results for lithium fluoride, silicon, gadolinium oxysulfide, and the active layer material of EBT2 (radiochromic film) were compared with the literature and a reasonable agreement was found. For a real patient treatment plan, the 3D distributions of s w,det in proton beams were calculated., Conclusions: Our method was validated by comparison with available literature data. Its equivalence with Bragg-Gray cavity theory was demonstrated mathematically. The capability of GATE-RTion v1.0 for the s w,det calculation at any point of a 3D dose distribution for simple and complex proton and carbon ion plans was presented., (© 2021 American Association of Physicists in Medicine.)

Four-dimensional dose calculation (4D-DC) is crucial for predicting the dosimetric outcome in the presence of intra-fractional organ motion. Time-resolved dosimetry can provide significant insights into 4D pencil beam scanning dose accumulation and is therefore irreplaceable for benchmarking 4D-DC. In this study a novel approach of time-resolved dosimetry using five PinPoint ionization chambers (ICs) embedded in an anthropomorphic dynamic phantom was employed and validated against beam delivery details. Beam intensity variations as well as the beam delivery time structure were well reflected with an accuracy comparable to the temporal resolution of the IC measurements. The 4D dosimetry approach was further applied for benchmarking the 4D-DC implemented in the RayStation 6.99 treatment planning system. Agreement between computed values and measurements was investigated for (i) partial doses based on individual breathing phases, and (ii) temporally distributed cumulative doses. For varied beam delivery and patient-related parameters the average unsigned dose difference for (i) was 0.04 ± 0.03 Gy over all considered IC measurement values, while the prescribed physical dose was 2 Gy. By implementing (ii), a strong effect of the dose gradient on measurement accuracy was observed. The gradient originated from scanned beam energy modulation and target motion transversal to the beam. Excluding measurements in the high gradient the relative dose difference between measurements and 4D-DCs for a given treatment plan at the end of delivery was 3.5% on average and 6.6% at maximum over measurement points inside the target. Overall, the agreement between 4D dose measurements in the moving phantom and retrospective 4D-DC was found to be comparable to the static dose differences for all delivery scenarios. The presented 4D-DC has been proven to be suitable for simulating treatment deliveries with various beam- as well as patient-specific parameters and can therefore be employed for dosimetric validation of different motion mitigation techniques.

Purpose: To present a reference Monte Carlo (MC) beam model developed in GATE/Geant4 for the MedAustron fixed beam line. The proposed model includes an absolute dose calibration in Dose-Area-Product (DAP) and it has been validated within clinical tolerances for non-isocentric treatments as routinely performed at MedAustron., Material and Methods: The proton beam model was parametrized at the nozzle entrance considering optic and energy properties of the pencil beam. The calibration in terms of absorbed dose to water was performed exploiting the relationship between number of particles and DAP by mean of a recent formalism. Typical longitudinal dose distribution parameters (range, distal penumbra and modulation) and transverse dose distribution parameters (spot sizes, field sizes and lateral penumbra) were evaluated. The model was validated in water, considering regular-shaped dose distribution as well as clinical plans delivered in non-isocentric conditions., Results: Simulated parameters agree with measurements within the clinical requirements at different air gaps. The agreement of distal and longitudinal dose distribution parameters is mostly better than 1 mm. The dose difference in reference conditions and for 3D dose delivery in water is within 0.5% and 1.2%, respectively. Clinical plans were reproduced within 3%., Conclusion: A full nozzle beam model for active scanning proton pencil beam is described using GATE/Geant4. Absolute dose calibration based on DAP formalism was implemented. The beam model is fully validated in water over a wide range of clinical scenarios and will be inserted as a reference tool for research and for independent dose calculation in the clinical routine., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: This paper describes the clinical implementation and medical commissioning of the MedAustron Particle Therapy Accelerator (MAPTA) for non-isocentric scanned proton beam treatments., Methods: Medical physics involvement during technical commissioning work is presented. Acceptance testing procedures, including advanced measurement methods of intra-spill beam variations, are defined. Beam monitor calibration using two independent methods based on a dose-area product formalism is described. Emphasis is given to the medical commissioning work and the specificities related to non-isocentric irradiation, since a key feature of MedAustron is the routine delivery of non-isocentric scanned proton beam treatments., Results: Key commissioning results and beam stability trend lines for more than 2 yr of clinical operation have been provided. Intra-spill beam range, size, and position variations were within specifications of 0.3 mm, 15%, and 0.5 mm, respectively. The agreement between two independent beam monitor calibration methods was better than 1.0%. Non-isocentric treatment delivery allowed lateral penumbra reduction of up to about 30%. Daily QA measurements of the beam range, size, position, and dose were always within 1 mm, 10%, 1 mm, and 2% from the baseline data, respectively., Conclusions: Non-isocentric treatments have been successfully implemented at MedAustron for routine scanned proton beam therapy using horizontal and vertical fixed beamlines. Up to now every patient was treated in non-isocentric conditions. The presented methodology to implement a new Scanned Ion Beam Delivery (SIBD) system into clinical routine for proton therapy may serve as a guidance for other centers., (© 2019 American Association of Physicists in Medicine.)

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer. Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created. Results: For CTV1, the average D median was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average D median was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D 2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D 2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams. Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Anthropomorphic phantoms mimicking organ and tumor motion of patients are essential for end-to-end testing of motion mitigation techniques in ion beam therapy. In this work a commissioning procedure developed with the in-house designed respiratory phantom ARDOS (Advanced Radiation DOSimetry system) is presented. The phantom was tested and benchmarked for 4D dose verification in proton therapy, which included: characterization of the tissue equivalent materials from computed tomography (CT) imaging, assessment of dose calculation accuracy in critical structures of the phantom, and testing various detectors for proton dosimetry in the ARDOS phantom. To prove the validity of the CT calibration curve, measured relative stopping powers (RSP) of the ARDOS materials were compared with values from CTs: original and overwritten with known material parameters. Override of rib- and soft-tissue phantom components improved RSP accuracy while inhomogeneous lung tissue, represented by the balsa wood, was better modelled by the CT Hounsfield units. Monte Carlo (MC) dose calculations were benchmarked against measurements with a reference Farmer chamber embedded in ARDOS material samples showing less than 3% relative dose difference. Differences between MC calculated dose distributions and those calculated by analytical algorithms for the ARDOS geometry were higher than 20% of the prescribed dose, depending on the position in the phantom. Pinpoint ionization chambers and thermoluminescence dosimeters showed differences of up to 5.5% compared to MC dose calculations for all lung setups in the static phantom. They were also able to detect dose distortions due to motion. EBT3 film dosimetry was shown to be suitable for 2D relative dose characterization, which could provide extended information on dose distributions in the penumbra area. The presented methodology and results can be used for drafting general recommendations for dynamic phantom commissioning, which is an essential step towards end-to-end evaluation of motion mitigation techniques in ion beam therapy.

This work describes the dosimetric commissioning of the treatment planning system (TPS) RayStation v6.1 from RaySearch Laboratories (Stockholm, Sweden) for a synchrotron-based scanned proton beam delivery with isocentric and non-isocentric setups at MedAustron. Focus was on the comparison of the pencil beam (PBv4.1) and Monte Carlo (MCv4.0) calculation algorithms. Commissioning of dose calculations was done first for 1D/2D dose delivery where the performance of the beam model in reproducing dosimetric properties for the delivery of single static pencil beams and mono-energetic layers with multiple spots was evaluated. The commissioning for 3D beam delivery employed test cases with increasing complexity: from box-shaped fields in homogeneous phantoms to the introduction of oblique incidences and inhomogeneities. Dose calculations were compared to the measured data for different air gaps and using beams with and without range shifter (RaShi). Depth-dose curves and spot shape comparisons showed good agreement of the results obtained with PBv4.1 and MCv4.0 algorithms at isocentric setup for open beam configurations (without RaShi). Comparison of transverse dose profiles for lateral heterogeneities at different depths showed better performance of the MCv4.0 algorithm in comparison to the PBv4.1 algorithm. In the case of 3D delivery comparisons of measured and TPS-calculated dose with MCv4.0 algorithm in box-shaped fields in water showed an average agreement within 2%. The results for dose calculations with the PBv4.1 algorithm showed larger deviations for beams with RaShi at all evaluated air gaps (from 64.8 cm to 14.8 cm). Our results suggest that the MCv4.0 algorithm shall be used in clinics for final dose calculation when beams with RaShi are used especially in the presence of large air gaps, inclined patient surface and lateral inhomogeneities. The detailed stepwise methodology implemented for the RayStation commissioning in this work could serve as further guidance for other facilities introducing a new TPS for proton beam therapy.

Purpose: The dose core of a proton pencil beam (PB) is enveloped by a low dose area reaching several centimeters off the central axis and containing a considerable amount of the dose. Adequate modeling of the different components of the PB profile is, therefore, required for accurate dose calculation. In this study, we experimentally validated one electromagnetic and two nuclear scattering models in GATE/Geant4 for dose calculation of proton beams in the therapeutic energy window (62-252 MeV) with and without range shifter (RaShi)., Methods: The multiple Coulomb scattering (MCS) model was validated by lateral dose core profiles measured for five energies at up to four depths from beam plateau to Bragg peak region. Nuclear halo profiles of single PBs were evaluated for three (62.4, 148.2, and 252.7 MeV) and two (97.4 and 124.7 MeV) energies, without and with RaShi, respectively. The influence of the dose core and nuclear halo on field sizes varying from 2-20 cm was evaluated by means of output factors (OFs), namely frame factors (FFs) and field size factors (FSFs), to quantify the relative increase of dose when increasing the field size., Results: The relative increase in the dose core width in the simulations deviated negligibly from measurements for depths until 80% of the beam range, but was overestimated by up to 0.2 mm in σ toward the end of range for all energies. The dose halo region of the lateral dose profile agreed well with measurements in the open beam configuration, but was notably overestimated in the deepest measurement plane of the highest energy or when the beam passed through the RaShi. The root-mean-square deviations (RMSDs) between the simulated and the measured FSFs were less than 1% at all depths, but were higher in the second half of the beam range as compared to the first half or when traversing the RaShi. The deviations in one of the two tested hadron physics lists originated mostly in elastic scattering. The RMSDs could be reduced by approximately a factor of two by exchanging the default elastic scattering cross sections for protons., Conclusions: GATE/Geant4 agreed satisfyingly with most measured quantities. MCS was systematically overestimated toward the end of the beam range. Contributions from nuclear scattering were overestimated when the beam traversed the RaShi or at the depths close to the end of the beam range without RaShi. Both, field size effects and calculation uncertainties, increased when the beam traversed the RaShi. Measured field size effects were almost negligible for beams up to medium energy and were highest for the highest energy beam without RaShi, but vice versa when traversing the RaShi., (© 2019 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

The characteristic depth-dose profile of protons traveling through material is the main advantage of proton therapy over conventional radiotherapy with photons or electrons. However, uncertainties regarding the range of the protons in human tissue prevent to exploit the full potential of proton therapy. Therefore, a non-invasive in-vivo dose monitoring is desired. At the ion beam center MedAustron in Wiener Neustadt/Austria, patient treatment with proton beams started in December 2016. A PET/CT is available in close vicinity of the treatment rooms, exclusively dedicated to offline PET monitoring directly after the therapeutic irradiation. Preparations for a patient study include workflow tests under realistic clinical conditions using two different phantoms, irradiated with protons prior to the scan in the PET/CT. GATE simulations of the C-11 production are used as basis for the prediction of the PET measurement. We present results from the workflow tests in comparison with simulation results, and by this, we demonstrate the applicability of the PET monitoring at the MedAustron facility., (Copyright © 2018. Published by Elsevier GmbH.)

The increased use of complex forms of radiotherapy using small-field photon and proton beams has invoked a growing interest in the use of micro-ionization chambers. In this study, 48 PTW-TM31015 PinPoint-type micro-ionization chambers that are used in the commissioning and patient specific QA of a proton pencil beam scanning (PBS) delivery system have been characterized in proton and high-energy photon beams. In both beam modalities, the entire set of PinPoint chambers was characterized by imaging them, by evaluating their stability using check source measurements, by experimentally determining the ion recombination, polarity effect and by cross calibrating them in terms of absorbed dose to water against Farmer-type ionization chambers. Beam quality correction factors were theoretically derived for both beam modalities. None of the chambers' check source readings drifted by more than 0.5% over a one year period. Beam quality correction factors for the 6 MV photon with reference to 60 Co were on average 1.0  ±  0.5% lower than the theoretical values calculated according to the data and procedures outlined in IAEA TRS-398. While this difference is within the overall dosimetric uncertainty, it is significant considering only uncorrelated uncertainties indicating inconsistencies in the theoretical data. Beam quality correction factors for the 179.2 MeV proton beam with reference to 60 Co were in good agreement with the theoretical data. Ion recombination and polarity correction factors were very consistent for all chambers with standard deviations of 0.2% or below show that findings from more comprehensive investigations in the literature can be considered as representative for all the chambers of this type. The characterization of 48 PinPoint-type micro-ionization chambers performed in this study provided a unique opportunity to investigate chamber-to-chamber variations of calibration, beam quality correction factors, ion recombination and polarity correction factors for an unprecedented sample size of chambers for both high-energy photon and proton beams.

Background and Purpose: Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres., Material and Methods: In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT., Results: All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods., Conclusions: Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study aims at selecting and evaluating a ripple filter design compatible with non-isocentric proton and carbon ion scanning beam treatment delivery for a compact nozzle. The use of non-isocentric treatments when the patient is shifted as close as possible towards the nozzle exit allows for a reduction in the air gap and thus an improvement in the quality of scanning proton beam treatment delivery. Reducing the air gap is less important for scanning carbon ions, but ripple filters are still necessary for scanning carbon ion beams to reduce the number of energy steps required to deliver homogeneous SOBP. The proper selection of ripple filters also allows a reduction in the possible transverse and depth-dose inhomogeneities that could appear in non-isocentric conditions in particular. A thorough review of existing ripple filter designs over the past 16 years is performed and a design for non-isocentric treatment delivery is presented. A unique ripple filter quality index (QIRiFi) independent of the particle type and energy and representative of the ratio between energy modulation and induced scattering is proposed. The Bragg peak width evaluated at the 80% dose level (BPW80) is proposed to relate the energy modulation of the delivered Bragg peaks and the energy layer step size allowing the production of homogeneous SOBP. Gate/Geant4 Monte Carlo simulations have been validated for carbon ion and ripple filter simulations based on measurements performed at CNAO and subsequently used for a detailed analysis of the proposed ripple filter design. A combination of two ripple filters in a series has been validated for non-isocentric delivery and did not show significant transverse and depth-dose inhomogeneities. Non-isocentric conditions allow a significant reduction in the spot size at the patient entrance (up to 350% and 200% for protons and carbon ions with range shifter, respectively), and therefore in the lateral penumbra in the patients.

Unlabelled: Anatomical changes in the head-and-neck (H&N) region during the course of treatment can cause deteriorated dose distributions. Different replanning strategies were investigated for volumetric modulated arc therapy (VMAT) and intensity-modulated proton therapy (IMPT)., Material and Methods: For six H&N patients two repeated computed tomography (CT) and magnetic resonance (MR) (CT1/MR1 at week 2 and CT2/MR2 at week 4) scans were acquired additionally to the initial planning CT/MR. Organs-at-risk (OARs) and three targets (CTV70Gy, CTV63Gy, CTV56Gy) were delineated on MRs and transferred to respective CT data set. Simultaneously integrated boost plans were created using VMAT (two arcs) and IMPT (four beams). To assess the need of replanning the initial VMAT and IMPT plans were recalculated on repeated CTs. Furthermore, VMAT and IMPT plans were replanned on the repeated CTs. A Demon algorithm was used for deformable registration of the repeated CTs with the initial CT and utilized for dose accumulation. Total dose estimations were performed to compare ART versus standard treatment strategies., Results: Dosimetric evaluation of recalculated plans on CT1 and CT2 showed increasing OAR doses for both, VMAT and IMPT. The target coverage of recalculated VMAT plans was considered acceptable in three cases, while for all IMPT plans it dropped. Adaptation of the treatment reduced D2% for brainstem by 6.7 Gy for VMAT and by 8 Gy for IMPT, for particular patients. These D2% reductions were reaching 9 Gy and 14 Gy for the spinal cord. ART improved target dose homogeneity, especially for protons, i.e. D2% decreased by up to 8 Gy while D98% increased by 1.2 Gy., Conclusion: ART showed benefits for both modalities. However, as IMPT is more conformal, the magnitude of dosimetric changes was more pronounced compared to VMAT. Large anatomic variations had a severe impact on treatment plan quality for both VMAT and IMPT. ART is justified in those cases irrespective of treatment modalities.

Unlabelled: In the current study IMPT plan robustness was evaluated with respect to inter-fractional patient positioning for various beam arrangements and two tumor indications in the cranial region., Material and Methods: For 14 patients suffering from tumors in the cranial region [skull base (SB; n = 7) and paranasal sinus (PS; n = 7)] the CTV and OARs were delineated. A safety margin of 3 mm was applied to the CTV. A prescribed dose of 2 GyE was planned via three beam arrangements (α, β, γ). Beam arrangement α consisted of lateral opposed fields for both tumor groups while beam arrangement β was optimized according to respective tumor and OAR locations, using two beams only. Beam arrangement γ applied four beams in the SB group and three beams in the PS group. Dose distributions were recalculated subjected to virtual patient translations along the major anatomical axes. The following dosimetric indices were evaluated and compared to original plans: target coverage (TC), target dose homogeneity (HI), CTV median and average dose (D(median), D(mean)). For OARs near maximum dose and average dose (D2%, D(mean)) were evaluated., Results: Dose distributions were distorted after introducing shifts. In the SB group, TC and HI were significantly different for caudal, cranial and anterior shifts for all beam arrangements. For PS patients, all but right shifts differed significantly from the original plans for all beam arrangements, although clinical relevance was not reached for arrangement γ (ΔTC < 1.5%). In general, beam arrangement γ exhibited the least spread of data regarding target indices and was consequently considered the most robust. Dosimetric parameters regarding the brainstem were mostly influenced by shifts along the anterio-posterior axis., Conclusion: For cranial IMPT, set-up uncertainties may lead to pronounced deterioration of dose distributions. According to our investigations, multi-beam arrangements were dosimetrically more robust and hence preferable over two beam arrangements.

Purpose: To investigate robust margin strategies in intensity modulated proton therapy to account for interfractional organ motion in prostate cancer., Methods and Materials: For 9 patients, one planning computed tomography (CT) scan and daily and weekly cone beam CTs (CBCTs) were acquired and coregistered. The following planning target volume (PTV) approaches were investigated: a clinical target volume (CTV) delineated on the planning CT (CTV(ct)) plus 10-mm margin (PTV(10mm)); a reduced PTV (PTV(Red)): CTV(ct) plus 5 mm in the left-right (LR) and anterior-posterior (AP) directions and 8 mm in the inferior-superior (IS) directions; and a PTV(Hull) method: the sum of CTV(ct) and CTVs from 5 CBCTs from the first week plus 3 mm in the LR and IS directions and 5 mm in the AP direction. For each approach, separate plans were calculated using a spot-scanning technique with 2 lateral fields., Results: Each approach achieved excellent target coverage. Differences were observed in volume receiving 98% of the prescribed dose (V(98%)) where PTV(Hull) and PTV(Red) results were superior to the PTV(10mm) concept. The PTV(Hull) approach was more robust to organ motion. The V(98%) for CTVs was 99.7%, whereas for PTV(Red) and PTV(10mm) plans, V(98%) was 98% and 96.1%, respectively. Doses to organs at risk were higher for PTV(Hull) and PTV(10mm) plans than for PTV(Red), but only differences between PTV(10mm) and PTV(Red) were significant., Conclusions: In terms of organ sparing, the PTV(10mm) method was inferior but not significantly different from the PTV(Red) and PTV(Hull) approaches. PTV(Hull) was most insensitive to target motion., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Purpose: The aim of the present study was to investigate potential dosimetric benefits of proton therapy for hypofractionated stereotactic body radiotherapy (SBRT)., Materials and Method: Twelve patients undergoing hypofractionated SBRT at the Medical University Vienna were selected. Passively scattered protons (PT) and intensity modulated proton therapy (IMPT) were evaluated against a conformal photon technique (3D-CRT), assuming a fractionation of 3x15Gy, prescribed to the 65% isodose. For all treatment techniques shallow breathing with abdominal compression (SB+AC) was compared with a deep inspiration breath hold technique (DIBH). Treatment planning was done with XiO (CMS, USA). Target conformity, dose-volume histograms (DVH) and various associated dosimetric parameters were considered for the planning target volume (PTV), lung, heart and esophagus., Results: For both breathing conditions conformity indices were very similar. They were between 0.75 and 0.78 for IMPT and 3D-CRT and around 0.55 for PT using 2-3 beams. Irrespective of treatment modality, DVHs for the ipsilateral lung were improved with the DIBH technique. For the PT technique, the 2Gy isodose (V2Gy) covered on average 7-9% less lung volume compared to 3D-CRT, for IMPT this reduction was more than 10%. Volumes covered the 4 and 6Gy isodoses were 2-4% smaller for IMPT, but very similar for PT and 3D-CRT. Both proton techniques achieved full sparing of the contralateral lung and superior sparing of the heart. Maximum doses to the heart and esophagus were on average around 3Gy for 3D-CRT and almost 0Gy for both proton techniques. For 3D-CRT average V2Gy values for the heart could be reduced from 64% in shallow breathing to 34% in DIBH. V2Gy for protons was negligible., Conclusions: Only small dosimetric differences were found between photons and protons for SBRT of lung lesions. Whether these small dosimetric benefits translate in reduced side effects or have the potential to improve local control rates remains to be demonstrated in clinical studies.

Poster: Physics track: Dose measurement and dose calculation PO-1410: Trend lines on patient specific quality assurance in ion beam therapy with protons and carbon ions M. Schafasand, G. Kragl, J. Osorio, S. Vatnitsky, M. Stock, A. Carlino. [Extracted from the article]